The pattern of linkage disequilibrium observed in a region of the genome is the residue of the history of mutation (and rarer events such as gene conversion), migration of subpopulations, recombination, and selection. Practically, in the search for associations between genetic variants and susceptibility to disease, linkage disequilibrium may be either a confounding factor obscuring which of a group of genes is responsible for the disease effect, or an essential tool, as in mapping by admixture linkage disequilibrium, enabling us to localize unknown disease genes to a small chromosomal region. We are currently involved in applying knowledge of the processes involved in the creation and persistance of linkage disequilibrium to develop tools to support the search for disease assocated genes. Our lab?s search for polymorphisms in AIDS candidate genes has uncovered several cases of genes with between two and nine polymorphic loci. Since all loci within a single gene will be recombinationally very close, strong linkage disequilibrium is the rule, and it is particularly interesting to consider the association of haplotypes, as well as of individual locus variants, on disease progression. In cases where a disease association has been observed, but the associated polymorphism may be only a marker for an as yet unidentified polymorphism, we can better focus the search for the functional polymorphism by narrowing down the association to specific haplotypes. Therefore we have developed a haplotype estimation program whose output includes code for survival analysis in the computer program, SAS, allowing rapid survival analysis with haplotypes as explanatory variables. On the genomic scale, we completed a study of 5048 autosomal short tandem repeat loci in homogeneous populations in the CEPH mapping pedigree, in an attempt to measure the ?background linkage disequilibrium? present in a panmictic human population. Approximately 4% of pairs of loci separated by less than 4 cM showed linkage disequilibrium, with the disequilibrium being proportional to the inverse of the recombination distance between the markers. A locus by locus 5cM sliding window analysis across 22 autosomes revealed 10 genomic segments (2.2-6.4 cM), of elevated multilocus linkage disequilibrium. These segments, which include HLA on chromosome 6, may be indicators of selective sweeps in recent evolutionary history, highlighting genome segments of particular evolutionary consequence. AIDS Resistance and Progression to AIDS - disease association, forensics, genetic differentiation, Genetic Diversity, Major histocompatibility Complex, microsatellites, Polymorphism, recombination, - Neither Human Subjects nor Human Tissues